Bettinger / Borenstein / Tao Microfluidic Cell Culture Systems

1. Auflage 2012
ISBN: 978-1-4377-3460-7
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 452 Seiten

Reihe: Micro and Nano Technologies

The fields of microfluidics and BioMEMS are significantly impacting cell biology research and applications through the application of engineering solutions to human disease and health problems. The dimensions of microfluidic channels are well suited to the physical scale of biological cells, and the many advantages of microfluidics make it an attractive platform for new techniques in biology. This new professional reference applies the techniques of microsystems to cell culture applications. The authors provide a thoroughly practical guide to the principles of microfluidic device design and operation and their application to cell culture techniques. The resulting book is crammed with strategies and techniques that can be immediately deployed in the lab. Equally, the insights into cell culture applications will provide those involved in traditional microfluidics and BioMEMS with an understanding of the specific demands and opportunities presented by biological applications. The goal is to guide new and interested researchers and technology developers to the important areas and state-of-the-practice strategies that will enhance the efficiency and value of their technologies, devices and biomedical products. - Provides insights into the design and development of microfluidic systems with a specific focus on cell culture applications - Focuses on strategies and techniques for the design and fabrication of microfluidic systems and devices for cell culture - Provides balanced coverage of microsystems engineering and bioengineering

Autoren/Hrsg.

Bettinger, Christopher

Borenstein, Jeffrey T

Tao, Sarah L

Leseproben

Preface
The concurrent emergence of microfabrication technologies and the biotechnology revolution have produced a vibrant intellectual landscape for the invention of new technologies to culture and manipulate cells using engineered in vitro environments. Advances in microfabrication, materials, and processing have provided a basis to design and control the presentation of multimodal cues to cells. Parallel advances in cell biology, gene sequencing, imaging, and microscopy empower scientists and engineers to extract rich data sets that aim to understand the inherent complexity of biology. There are several motivating factors for productive interdisciplinary research activities at the intersection of microfabrication technologies with cell culture strategies. First, the ability to manipulate fluids with a high degree of precision is highly advantageous. This is accomplished through novel materials and new micron-scale fluid handling components such as pumps, mixers, and valves. In addition, systems with a characteristic length scale of microns ensure ordered laminar flow, which can expedite mixing and separation of fluids. Another important reason for the productive interaction between microfabrication and cell culture technologies lies in the congruence of length scales. Microfabrication techniques are able to create unique structures that can achieve cellular and subcellular dimensions. These structures can be used to manipulate cells and their organelles with a high degree of precision. Nanometer-scale structures can be used in parallel to influence related processes such as protein adsorption and cellular processes such as adhesion and migration. When combined with additional advances in biotechnology, cell biology, and tissue engineering, microfabrication technologies have the potential to broadly impact many aspects of biomedical engineering. New fundamental knowledge may be gained through hypothesis-driven research that is enabled by precise control of the cellular microenvironment. Technological advances and discovery-driven research may include engineering new tissue constructs for potential applications in regenerative medicine and drug discovery. These and related topics will be the primary focus of this text. The development of new small molecules and biologics for therapeutic applications has slowed significantly in recent years, due in large part to limitations in existing approaches for assessing the safety and efficacy of these compounds in preclinical models. Conventional cell culture assays and animal models have historically provided the foundation for preclinical models, but each suffers from shortcomings that may be overcome by the emergence of new technologies. Species differences present an enormous challenge for toxicity evaluation in preclinical studies, but conventional cell culture assays using human primary cells or stem cells in two-dimensional formats that do not replicate organ microenvironment and do not incorporate interactions between tissues and organs are likewise not sufficiently predictive of clinical responses [1]. Therefore, the opportunity exists to incorporate human-derived cells in three-dimensional microenvironments representative of tissue and organ physiology, and further to integrate these functional units to reflect organ crosstalk, in a manner that enables more rapid, efficient, and accurate preclinical assessment of emerging molecular compounds, biologics, and other medical countermeasures [2]. The emergence of microscale fabrication tools enables the construction of three-dimensional microenvironments that are more representative of tissue and organ physiology in appropriate dimensional scales [3], while microfluidic techniques provide the capability to control critical functions such as dosing and sampling in these systems. These new capabilities are clearly of great interest to industrial researchers in the pharmaceuticals and biologics industry, but also to the US Department of Defense and the Department of Health and Human Services as part of a broader national initiative aimed at bolstering capabilities for dealing with emerging infectious diseases and bioengineered threats [4]. Ultimately, it is envisioned that these microphysiological systems will contribute to dramatic reductions in the cost and time required to develop and assess the safety and efficacy of new treatments for a host of diseases ranging from cancer to pandemic influenza outbreaks. The focus of this book is to demonstrate the potential for rational material design in solving a diverse range of biomedical problems where the functional utility of cells and tissues are cornerstones. As such, the book is divided into three sections, comprising 17 chapters written by recognized experts from leading groups around the world. It covers a spectrum of topics and highlights more recent work that represents the current state of the art in the field. The first section of the book is intended to blend elements of theory and key concepts with novel materials and fabrication techniques to impart physiological relevance of microfluidic systems. The second and third sections are designed to demonstrate further how these microfluidic principles can be utilized for two distinct applications, tissue engineering strategies and in vitro systems. Each of these applications requires a unique microfluidic toolset. Through the examples presented, it is demonstrated that microfluidics can provide highly controlled microenvironments which can be utilized to regulate cell behavior in a variety of applications from the recapitulation of native tissues for clinical therapies to high-throughput screening systems which are scalable and easy to operate. The enabling nature of microfluidic technology may result in numerous future advances in basic biological understanding, clinical therapeutics, and diagnostics. The sections of the book are organized as follows: • Materials and Fabrication Methods Materials and associated microfabrication processes form the cornerstone for advanced microfluidic devices that are dedicated for cell culture applications. These two essential topics are discussed concurrently in this section. One prevalent theme is the evolution of materials that are used in microfluidic devices. The composition of microfluidic devices has gradually migrated from traditional engineering polymers toward biopolymers. Novel materials require new materials processing and fabrication strategies to produce biologically relevant microfluidic devices. Microfluidic devices with biologically active materials and biomimetic structures can be designed to influence cell behavior through the coordinated presentation of multimodal cues such as mechanical properties, integrin-binding domains, topographic structures, and soluble factors. These considerations and related topics will be the subject of this section. • Tissue Engineering Strategies Tissue engineering is the process in which engineering principles are utilized to assemble cells for the purpose of forming new tissues. Over the past few decades, the field has focused on design of both synthetic and native materials to direct cells toward formation of physiologically relevant tissues. In this section, the use of microfluidic technologies in tissue engineering applications is explored. Two major concepts are examined through the examples outlined in these chapters. First is the use of microfluidics to dynamically manipulate the chemical and mechanical cellular environment in order to direct and regulate cellular behavior. Second is the use of microfluidics to serve as perfusion networks to sustain long-term culture of engineered tissues through continuous flow of oxygen, nutrients, or withdrawal of waste products. The utility of microfluidics in tissue engineering is delineated in this section through specific tissues including vascular, pulmonary, and kidney. • In Vitro Models Emerging in vitro models for specific tissue and organ systems such as the liver and cardiovascular system, and tools aimed at assessing dynamic processes within these systems, are the focus of this section. Microfluidic approaches capable of mimicking the microstructure of the liver and the specific arrangement and interactions involving liver parenchyma are described, and microscale techniques for manipulating and sorting cells and applying shear dynamics to cell populations are also covered. Another area undergoing rapid development is the use of microfluidic approaches to generate gradients and flows within physiologically relevant matrix materials to simulate processes such as angiogenesis and metastasis. These and related topics are also covered in this section. We hope that our readers find this book to be a useful and stimulating reference that provides key information regarding the application of microfluidic technologies toward cell culture and tissue engineering applications, and we would like to thank all of our authors for sharing their recent results and advances in this exciting and potentially transformative field. Jeffrey T. Borenstein References
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